title: Protection from carcinogen-induced murine bladder carcinoma by interferons and an oral interferon-inducing pyrimidinone, bropirimine.
abstract: Interferons (IFNs) have established activities as antivirals and inhibitors of viral and transplantable tumors. To establish whether IFNs or their inducers can affect induction of carcinogenesis in vivo, the bladder-specific carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was administered in the diet at 0.11 or 0.13% (w/w) to female C3H/He mice beginning at 7 weeks of age. Mice treated with the IFN-inducing bropirimine [2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone] i.p. twice a week for 14 weeks starting on day 30 of start of FANFT feeding developed fewer transitional cell carcinomas (TCC) than mice treated with the vehicle. Bropirimine (200 mg/kg twice a week) orally resulted in even greater effectiveness: 6 of 43 bladders with TCC for bropirimine-treated mice versus 24 of 39 for control glycine buffer-treated mice (P less than 0.01, x2 test). Mice treated i.p. daily on days 29 through 210 with 5,000 units of beta interferon (specific activity, 2.0 x 10(8) units/mg) had 0 of 15 TCC while control mice had 7 of 13 TCC (P less than 0.001). Bladders of untreated mice were also significantly heavier than those of beta interferon- or bropirimine-treated mice. This dose of IFN treatment was confirmed as effective in a second experiment, in which mice were treated daily on days 30-223 with 5,000 units alpha/beta interferon (specific activity, 1.2 x 10(7) units/mg). This resulted in 4 of 25 bladders with TCC versus 24 of 39 for control mice (P less than 0.001). A higher dose of IFN (50,000 units alpha/beta interferon daily) was toxic; 24 of 30 mice died within 2 months. IFN and an IFN inducer, bropirimine, inhibited development and progression of FANFT-induced bladder TCC in vivo and thus may have roles as chemopreventive modalities.
authors.affiliation: Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
authors.forename: E C
authors.initials: EC
authors.lastname: Borden
authors.forename: Y A
authors.initials: YA
authors.lastname: Sidky
authors.forename: E
authors.initials: E
authors.lastname: Ertürk
authors.forename: W
authors.initials: W
authors.lastname: Wierenga
authors.forename: G T
authors.initials: GT
authors.lastname: Bryan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000517:prevention & control*; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005200:FANFT; D005260:Female; D007369:Interferon Inducers / Q000008:administration & dosage / Q000627:therapeutic use*; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D007369:Interferon Inducers; D007370:Interferon Type I; D005200:FANFT; D003596:Cytosine; C033560:bropirimine